This invention relates to an economical one-step decarboxylation process to substitute iodine atoms for silver carboxylate radicals using silver salts of aromatic and heterocyclic carboxylic acids in a solventless procedure.
Usually a decarboxylation reaction results in the generation of carbon dioxide and the concurrent replacement with hydrogen on the molecule. For example, the decarboxylation of benzoic acid yields benzene and carbon dioxide. Pyridine carboxylic acid goes to pyridine and carbon dioxide. The presence of other carboxylic acid salts such as a sodium carboxylate of an aromatic acid will merely aid in the decarboxylation reaction and char to yield an ill-defined residue at best. However, the decarboxylation products using silver salts of carboxylic acids are silver, carbon dioxide and the coupled organic radicals of the silver carboxylates in the form of dimers, trimers, and multiples thereof. Surprisingly also, if the decarboxylation reaction takes place in the presence of iodine the decarboxylation process forms organic iodides of the reactant silver salt in a one-step process. My invention works because the use of solvents is avoided and the silver salts are heated directly with the iodine.
Among the procedures which exist for reacting halogens with the silver salts of carboxylic acids are the solvent-using Hunsdieker and Simonini reactions, as well as variations of these two reactions developed by other investigators such as Oldham and Prevost. The halogen used, the ratio of silver salt to halogen, the presence or absence of other active materials such as olefins, acetylenes or readily substituted aromatic rings and the solvent used are well-known to play a large part in determining the course of these reactions. (C. V. Wilson, Organic Reactions, IX, p. 332-387 (1957)) Thus, it is possible by these solvent reactions to produce organic halides containing one less carbon atom than the original acid RCOOH, (the Hunsdieker reaction); esters, RCOOR, derived from two molecules of the acid by loss of one molecule of carbon dioxide (the Simonini reaction); and halogenated aromatic compounds, XRCOOH, where X is a halogen and R is a phenyl group. These reactions can be represented by the following equations. EQU RCOOAg + X.sub.2 .fwdarw. RX + CO.sub.2 + AgX A. EQU 2RCOOAg + X.sub.2 .fwdarw. RCOOR + CO.sub.2 + 2AgX B. EQU 3RCOOAg + 2H.sub.2 .fwdarw. RCOOR + RX + 2CO.sub.2 + 3AgX C. EQU RCOOAg + X.sub.2 .fwdarw. XRCOOH + AgX D.
The reaction represented by A in which the molar silver salt-halogen ratio is 1:1 is the Hunsdieker reaction. The B reaction is the Simonini reaction and uses a 2:1 mole ratio of silver salt to halogen (iodine only). Reaction C is a variation of A and B by Oldham and Ubbelodhe and uses a 3:2 molar ratio. Reaction D is a variation of A and requires the presence of a phenyl group which undergoes electrophilic substitution readily.
The Hunsdieker and Simonini reactions, and the variations of these reactions developed by other investigators generally utilize non-reacting solvents. Carbon tetrachloride is considered the best general solvent for the Hunsdieker reaction. The other reactions can use benzene, carbon tetrachloride, petroleum ether, nitrobenzene or ether, as well as other solvents. The reactants are heated in a suitable solvent to cause the desired reaction.
The value of the Hunsdieker reaction in which the silver salt-halogen molar ratio is 1:1 lies in its application to aliphatic bromine compounds where it is a general preparative method. A substituent in the aliphatic chain in any position other than the .alpha.-position does not interfere with the reaction unless it is itself capable of reaction with the acyl hypohalite. In the aromatic series, the Hunsdieker reaction is not so general. Bromobenzene is formed from silver benzoate but the yields are variable and are apparently dependent upon the temperature. Although many Hunsdieker reactions involving aliphatic compounds have been described (D. I. Davies and S. J. Cristol, Adv. In Free Radical Chem., I, 180-184 (1965); J. W. Oldham and A. R. Ubbelohde, J. Chem. Soc., 368 (1941)), the Hunsdieker reaction has not been reported as giving good yields with aromatic compounds. For example, silver benzoate reacted with iodine to give only a 14% yield of iodobenzene, but no iodide was formed from silver p-nitrobenzoate. (R. A. Barnes and R. J. Prochaska, J. Am. Chem., Soc. 72, 3188, (1950)). The Simonini reaction has been reported categorically (C. V. Wilson, op. cit., 349) as having no value in the aromatic series. Silver benzoate gives a variety of products including the ester, the halide and halogenated benzoic acid. Silver phthalate gives phthalic anhydride.
It is, therefore, a general object of my invention to provide a new process for making aromatic and heterocyclic iodides in good yields in a convenient and economic manner using a general reaction. Another object of my invention is to provide a new process for converting silver derivatives of carboxylic acids to iodides, replacing the carboxylic acid group by a halogen. A further object of my invention is to provide a practical and economic process for the manufacture of mono and polyiodo aromatic and heterocyclic compounds directly from aromatic and heterocyclic compounds. The nature of still other objects of my invention will be apparent from a consideration of the descriptive portion to follow.
It is my discovery that the above and other objects of the invention are attained by the solventless silver salt/iodine process herein described. I have found that aromatic and heterocyclic silver salts react with iodine without the presence of solvents to yield organic iodo and polyiodo compounds. This is quite surprising inasmuch as reactions generally go better in solvents and improved yields usually result when a suitable solvent is found.